Treating Early-Stage CKD With New Medication

Therapies: Results of a CKD Patient Survey Informing the 2020 NKF-FDA Scientific Workshop on Clinical Trial Considerations for Developing Treatments for Early Stages of Common, Chronic Kidney Diseases

Rationale & Objective: With a growing number of medications and therapies available to treat chronic kidney disease (CKD), risk-versus-benefit discussions are increasingly critical. Balancing risks and benefits requires assessing patients' understanding of these, as well as incorporating patient preferences and tolerance for side effects into shared decision-making. 

Study Design: A 26-question online survey was sent to people in the National Kidney Foundation patient email list and posted on associated social media pages to assess the respondents' willingness and comfort with taking preventative medications during earlier-stage CKD to inform a December 2020 scientific workshop co-sponsored by the National Kidney Foundation and the US Food and Drug Administration on clinical trial considerations in developing treatments for individuals with early stages of CKD. 

Setting & Population: Online survey of CKD patients, including broad demographic data and responses to risk-benefit scenarios, with surveys emailed to 20,249 people not identified as currently receiving kidney replacement therapy. 

Analytical Approach: Survey results are presented as descriptive data.

 NEW HERBAL-CISTANCHE THERAPIES AVAILABLE TO TREAT CHRONIC KIDNEY DISEASE

Results: Of 1,029 respondents, 45 self-identified as at risk for CKD, 566 had CKD, 267 had received kidney transplants, 51 were receiving dialysis, and 100 replied other or did not answer. Respondents reported being willing to assume some risk to prevent the progression of CKD, with a greater willingness to assume risk and treatment burdens the closer they came to late-stage disease. Clinician recommendations regarding kidney therapies and clinician willingness to work with patients to address any side effects were important in respondents' willingness to initiate and persevere with a new medication.

Limitations: Approximately 10% response rate with limited data on respondents. 

Conclusions: Risk-versus-benefit discussions appear key to patients and their care partners making well-informed decisions about taking a new medication that may or may not help the progression of their kidney disease. Future tools and strategies are needed to facilitate informed discussions of treatment in early-stage kidney disease.

Chronic kidney disease (CKD) is a major public health problem affecting an estimated 37 million American adults.1 Most people with CKD are unaware of their disease, even those with more advanced disease.2 Kidney failure requiring kidney replacement therapy is a relatively uncommon outcome, with a lifetime risk of approximately 3%-4%, although this is higher, approaching 8%-9%, among those of African ancestry.3-5 Moreover, one-third of US residents develop advanced CKD (defined as a glomerular filtration rate [GFR] <45 mL/min, consistent with CKD stage 3b), with a significant impact on overall health, including increased risk of cardiovascular disease, cognitive impairment, anemia, and mineral and bone disorders.4,6 All of this contributes to the high utilization of health care resources; high costs to governments, insurers, and individuals; and lost productivity with worse quality and duration of life.

In the past 2 decades, there have been significant advances in basic and clinical science related to CKD progression, including validation of surrogates for hard clinical endpoints that can be used in clinical trials of new CKD treatments, even early in the disease course.7,8 Recent approval of medicines to prevent the progression in later stages of CKD, as well as the use of surrogate endpoints in rare diseases with newer, disease-specific interventions, have established an environment that is primed for the development and evaluation of treatments for common causes of CKD early in the disease course.9-11

Medications targeting kidney disease will only benefit a subset of individuals with or at risk of early-stage CKD, raising the question of who should receive the medications and when they should be received in the course of the disease. While risk prediction tools may improve the selection of those patients most likely to benefit from interventions that decrease the risk of CKD progression, there is still much to learn about why some patients progress and others do not and, in the absence of precise risk estimates, patients may not be able to quantify their risk to weigh benefits of early treatment. In light of these factors, compounded with patients' unique comorbid conditions, circumstances, and value preferences, it is not surprising that risk-versus-benefit conversations among clinicians, patients, and care partners are challenging.12-15 Given this, there is a clear imperative to assess peoples' willingness and comfort with taking preventative medications in earlier-stage CKD. As no therapy is without side effects, it is particularly important to capture concerns regarding side effects that may have an impact on willingness to take a medication.

PLAIN-LANGUAGE SUMMARY

The goal of the survey was to gain insight into patient preferences and considerations for determining how much risk (side effects) versus potential future benefits (slowing progression of chronic kidney disease [CKD]) they would be willing to accept when taking a new medication. The results of the survey informed a scientific workshop on clinical trial considerations in developing treatments for the early stages of CKD cosponsored by the National Kidney Foundation and the US Food and Drug Administration in December 2020. 

The results showed that there was a willingness to assume risk in seeking treatment to slow the progression of kidney disease, which highlighted the need for more frequent and earlier education about the risk of CKD progression and the potential benefits of early-stage treatment.

In December 2020, the National Kidney Foundation (NKF) and the US Food and Drug Administration (FDA) co-sponsored a scientific workshop to explore patients', providers', and payers' perceptions of the value of treating early CKD. To inform this workshop, NKF surveyed their patient network on patient perspectives regarding their risk of kidney disease progression, as well as considerations important to patients in deciding whether or not to take new medications that could reduce their risk of progression.

METHODS 

This observational survey aimed to assess the baseline knowledge of CKD, the level of understanding of respondents' current CKD status, and perceptions of the future risk of progression either to late-stage CKD or kidney failure. Additionally, survey questions were aimed at identifying individuals' values and considerations in decision-making about taking a medication that may or may not benefit them. This anonymized survey with minimal demographic data was designed to inform the conference proceedings and was not intended to develop generalizable knowledge; therefore, informed consent was not obtained. Survey Development The 26-question survey was developed with input from the conference planning committee, which included the researcher, clinician, patient, and regulatory members (Items S1 and S2). The planning committee first identified key topics that they thought would be critical to inform conference participants, including knowledge of CKD and the individual respondent's current health, perception of their future kidney health risk and progression, and the value placed on minimizing side effects from medications to prevent progression. 

We used existing validated surveys to assess respondents' knowledge about kidney disease and related signs or symptoms that a person might experience if they have advanced CKD or kidney failure.16 We reviewed a survey distributed to the heart-failure patient community before a similar conference.17 Drafts of the survey were then shared with patient reviewers from the NKF's Kidney Advocacy Committee, and edits were made based on their feedback and insights. To assess perspectives around the risks and benefits of taking a new medication, we developed scenarios that asked respondents to consider whether they would take a new medication that would reduce their risk of developing kidney failure over the next 20, 10, and 5 years, framed with the assumption that they had a 20% risk of developing kidney failure over those periods. The time frame was selected based on a review of the literature, which describes progression rates in CKD populations that range from 2 to 5 mL/min per year.18,19 For example, for a patient starting at a GFR of 70 mL/min per 1.73 m2, the patient would be at CKD stage 5 after 20 years. Responses to risk questions were ranked on a 5-point scale ranging from not likely to very likely. To assess perspectives on the tolerance of specific medications, we asked respondents to consider specific benefits and side effects, including how these side effects would impact their willingness to take the medication and how important certain factors are in deciding to take a new medication. We developed the list based both on common side effects for medications used in general (constipation) and for CKD (dizziness, increased urination), including known sodium/glucose cotransporter 2 side effects (increased urination, urinary tract infections).20 Many medications require monitoring and more frequent appointments and blood tests. Responses to these questions had 3 possible response choices: not important, important, or very important.